The FDA's Oncologic Drugs Advisory Committee voted 7-4, with two panelists abstaining, that the benefits outweigh the risks for vincristine sulfate liposomal injection for the treatment of adult patients with Philadelphia chromosome negative (Ph-) acute lymphoblastic leukemia (ALL) in second or greater relapse or who have failed at least two prior treatments with other anti-leukemia drugs. There is currently no FDA-approved drug treatment for this specific group of patients.

Adult ALL is one of the rarest types of cancer -- there are about 2,000 new cases of adult ALL diagnosed each year in the U.S. (the disease mostly affects children). Of those cases, 1,400 are Ph- ALL. The five-year survival rate for all adults with relapsed Ph- ALL is just 7%.

Although panelists were only lukewarm about data presented by Talon Pharmaceuticals, the maker of vincristine sulfate liposomal injection, most felt having the option for patients was better than not having the option. If the FDA agrees with the panel's decision, it would then grant the drug an accelerated approval, which would allow it to come to market even as the company was performing another study to prove the drug really works. If that study failed, the FDA could revoke its approval.

Vincristine is an agent currently used in multi-agent chemotherapy treatments. Talon is seeking approval for vincristine sulfate liposomal injection, or VSLI for short, as a monotherapy injectable form of the drug. Giving the drug via injection means the patient doesn't have to spend time in the hospital receiving multi-agent chemotherapy.

On Wednesday morning, the panel reviewed Talon's phase II single-arm, open-label, dose-escalation trial of 65 Ph- ALL patients who had failed two or more previous anti-leukemia treatments. The study's endpoint was rate of complete remission with or without complete blood count recovery (known as CR+CRi).

Ten of the 65 patients (15.4%) achieved complete remission (judged by an examination of bone marrow) that lasted for a median of 28 days.

Talon pointed to another endpoint in its briefing documents: Median overall survival in the entire population treated was 4.6 months, while those who achieved CR+CRi lived an average of 7.7 months. Some panelists seemed hopeful that patients who achieve CR+CRi with vincristine sulfate liposomal injection could become well enough to undergo a hematopoietic stem cell transplantation.

Although the outcome data might sound bleak -- especially considering that only five patients lived more than a year after their last dose of VSLI -- Talon said that patients who have relapsed after trying one or two previous treatments generally live no more than three months, while patients who are on their third or fourth relapse generally live only a few weeks.

There was debate over whether the drug was shown to possibly work better than multi-chemotherapy agents (although the company's trial did not test that).

Panelist Frank Balis, MD, an oncologist at the Children's Hospital of Philadelphia, wasn't convinced by the data and voted against recommending approval. "I don't see a benefit to placing this already-known agent into a new delivery package," he said.

More than three-quarters of patients reported a serious adverse event during treatment, often neuropathy. However, about 80% of the patients in the study had residual vincristine-associated neuropathy from earlier treatments with multi-agent chemotherapy that included vincristine.

The majority of the panelists thought the drug's toxicities might be less than those of multi-agent chemotherapy.

The FDA is not required to follow the advice of its advisory committee, but it often does. If the FDA approves vincristine sulfate liposomal injection, Talon would be required to conduct a phase III trial testing the drug against multi-agent chemotherapy in at least 348 elderly patients with newly diagnosed ALL.

MedPageToday is a trusted and reliable source for clinical and policy coverage that directly affects the lives and practices of health care professionals.

Physicians and other healthcare professionals may also receive Continuing Medical Education (CME) and Continuing Education (CE) credits at no cost for participating in MedPage Today-hosted educational activities.